Detection of gingipain activity using solid state nanopore sensorsShow others and affiliations
2022 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 368, article id 132209Article in journal (Refereed) Published
Abstract [en]
Accurate, robust, and rapid diagnostics is the basis for all well-functioning healthcare. There is a large need in point-of-care biosensors to facilitate diagnosis and reduce the need for cumbersome laboratory equipment. Proteases are key virulence factors in periodontitis. Periodontal disease is very common and characterized by inflammation and infection in the tooth-supporting structures and is linked to many systemic diseases such as cardiovascular disease, diabetes, and Alzheimer's disease. Proteases present in periodontal disease, gingipains, are highly responsible for the disease onset and progression and are therefore a promising biomarker. Here we show a novel nanopore-based biosensor strategy for protease activity monitoring. Solid-state nanopores were modified with a proteolytic substrate, restricting the ionic current through the apertures of the nanopores. Protease can digest the proteolytic substrate thus enlarge the aperture and the ionic current. Trypsin was used as an initial model protease to investigate the performance of the sensor. We show that the solid-state nanoporebiosensor can detect trypsin with a limit of detection (LOD) of 0.005 ng/mL (0.2 pM). The detection system developed for the model enzyme was then applied to the detection of gingipains. The LOD for detection of gingipains was 1 ng/mL (0.02 nM), with a 27% recovery of the signal at 0.1 mu g/mL, indicating that the sensitivity and dynamic range are relevant for the clinical diagnosis of periodontitis. The generic detection of protease activity and high sensitivity make this a promising sensor technology for both diagnosis of periodontal disease and monitoring of other disease-related proteases.
Place, publisher, year, edition, pages
Elsevier, 2022. Vol. 368, article id 132209
Keywords [en]
Biosensor, Solid-state nanopore, Pore blocking, Pore opening, Trypsin, Enzyme detection, Gingipains
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:oru:diva-100420DOI: 10.1016/j.snb.2022.132209ISI: 000829536400001Scopus ID: 2-s2.0-85132315321OAI: oai:DiVA.org:oru-100420DiVA, id: diva2:1685723
Funder
Swedish Foundation for Strategic Research, FFL15-0174 FFL15-0026Swedish Research Council, 2019-04690 2017-04475 2016-04874Swedish Cancer Society, CAN 2017/430
Note
Funding agency:
Wallenberg Academy Fellow Program KAW 2020.0190 KAW 2016.0231
2022-08-042022-08-042024-03-21Bibliographically approved
In thesis